Acute herpes simplex virus (HSV) infection of the eye in human frequently proceeds to a latent state. Recurrence of HSV involving the corneal stroma layers presents a difficult clinical problem for the ophthalmologist to control. Ocular HSV is the most serious and most prevalent infectious cause of corneal blindness in the United States. The overall objective of this proposal is to elucidate (1) The mechanisms of acute, latent and recurrent HSV-induced ocular disease, and (2) Virus-related factor which may be responsible for the more severe forms of herpetic disease. Acycloguanosine (ACG) is a new antiviral drug which is taken up selectively and specifically activated by HSV-infected cells. Radiolabelled ACG has been used as a tag or marker for HSV-infected tissue. The combination of selectivity and specificity displayed by ACG (radiolabelled) coupled with the sensitivity of autoradiographic techniques provides a novel approach for studying ocular herpetic disease. The progression of ocular herpetic keratitis induced by HSV strains with known clinical histories of pathogenicity will be compared by transmission electron microscopic and light microscopic autoradiographic studies. Several HSV strains with predictable ocular pathogenicity patterns will be compared following multiple in vitro passages in either corneal epithelium, stromal keratocytes or endothelium cell cultures. The virus-eye related properties to be studied includes the following: (1) Virus adaptation to corneal derived cell cultures; (2) Basis for stromal tropism and cell death; and (3) Virus affinity for specific corneal cells. The in vivo evaluation of ACG will be performed in rabbits with acute herpetic corneal disease, and recurrent herpetic eye disease.